Evidence map›Paper›PMID 40318978›Full record

ArticleAnnals of the rheumatic diseases2025

Functional dissection of noncoding variants associated with rheumatoid arthritis.

Ajay Jajodia, Arpit Mishra, Naresh Doni Jayavelu, Katharina Lambert, Nicholas Moss, Zongchen Yang, Karen Cerosaletti, Jane H Buckner, R David Hawkins

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Article in Annals of the rheumatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Ajay JajodiaDivision of Medical Genetics, Department of Medicine, Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Arpit MishraDivision of Medical Genetics, Department of Medicine, Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Naresh Doni JayaveluDivision of Medical Genetics, Department of Medicine, Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Katharina LambertBenaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Nicholas MossDivision of Medical Genetics, Department of Medicine, Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Zongchen YangDivision of Medical Genetics, Department of Medicine, Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Karen CerosalettiBenaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Jane H BucknerBenaroya Research Institute at Virginia Mason, Seattle, WA, USA.
R David HawkinsDivision of Medical Genetics, Department of Medicine, Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Benaroya Research Institute at Virginia Mason, Seattle, WA, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: rdhawk@uw.edu.

Funding

Functional validation of Rheumatoid Arthritis-associated distal regulatory SNPs iR01AR065952 · NIAMS · UNIVERSITY OF WASHINGTON · PI HAWKINS, RAYMOND DAVID · 2015 to 2018
$1.8M
NIAMS NIH HHS R01 AR065952
6 · The paper itself

Abstract

objectivesNoncoding variants are critical to our understanding of the genetic basis of diseases and disorders such as rheumatoid arthritis (RA). While genome-wide association studies have identified regions of the genome associated with disease, functional studies are still lagging that can identify potentially causative variants.

methodsIn order to functionally fine-map RA-associated variants, we identified variants at enhancers marked in primary activated T helper cells and conducted massively parallel reporter assay in these cells.

resultsWe found that combinations of functional variant genotypes are often exclusive to patients with RA. We leveraged 3-dimensional genome architecture and expression quantitative trait loci data to identify target genes of enhancers exhibiting allelic differences in activity. We confirmed enhancer activity and target gene interactions by Clustered Regularly Interpaced Short Palindromic Repeats Cas9 (CRISPR-Cas9) deletion in primary T cells.

conclusionsThe identification of functional enhancer variants suggests possible causal variants, and their target genes reveal known and novel genes as likely drivers of RA, as well as a means for therapeutic intervention.

Indexed as

Arthritis, RheumatoidEnhancer Elements, GeneticGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyGenotypeHumansPolymorphism, Single NucleotideQuantitative Trait Loci

Identifiers

PMID40318978
PMCPMC13127724

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